Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematologic disorders characterized by ineffective hematopoiesis and dysplasia. It is a hematological disorder in which genomic abnormalities accumulate in a hematopoietic stem cell leading to peripheral cytopenias of varying degrees of severity, as a consequence of multilineage differentiation impairment, and, in the early phases, bone marrow (BM) apoptosis. Morbidity and mortality in the disease results from cytopenias or transformation to acute myeloid leukemia, which may both lead to serious infectious diseases, anemia or hemorrhage caused by dysfunction and reduction of blood cells. There are associated cytogenetic abnormalities, including deletions of chromosomes 5, 7, amongst others.
The diagnosis of MDS currently requires a multidisciplinary approach involving hematologic, morphologic and cytogenetic analyses, and may be difficult to render, owing to the fact that at least 50% of patients present with one or fewer cytopenias and only about 50% of patients demonstrate cytogenetic abnormalities. The choice of therapies used to treat MDS heavily depends on disease severity and the risk of progression to more advanced disease. The ability to accurately predict prognosis is therefore an essential component of patient care. Currently used prognostic scoring systems consider karyotypic abnormalities and certain clinical features to stratify MDS patients into risk groups. Some karyotypic abnormalities, such as deletion of chromosome 5q, help establish prognosis and can be associated with a specific clinical phenotype.1 However, more than 50% of MDS patients have a normal karyotype, and patients with identical chromosomal abnormalities remain clinically heterogeneous.2,3 Single gene mutations are not currently employed in prognostic scoring systems, but are likely to be key drivers of clinical phenotypes and overall survival (OS).4-6 Understanding the clinical impact of mutations in different genes could improve the prediction of prognosis for patients with MDS and inform selection of specific therapies.